Preimplantation genetic screening (PGS) has been available for IVF patients for over a decade now and allows for the transfer of the best and the most healthy embryos first. However, as with all new technologies, it has as many supporters as opponents. The webinar host is Dr Benjamin Abramov, the Medical Director at GENNET City Fertility who reviews all the information concerning PGS and answers the basic question: is genetic embryo screening really worth it?
Dr Abramov starts with describing the standard routine of IVF treatment. In IVF treatment without PGS, patients very often have a number of embryos they need to make a decision about. They have to decide whether these day-3 or day-5 embryos should be retransplanted. The decision is made on the basis of observational parameters, in other words: how well does the embryo look under the microscope. With PGS however you make that decision on the basis of whether the embryo has got a normal makeup of chromosomes. The morphological grading comes second.
Dr Abramov goes on to clarify the terms PGS and PGT-A. It turns out that PGS and PGT-A refer to the exactly the same thing and the exact same technology. PGT-A stands for pre-implantation genetic testing for aneuploidies. PGS is an acronym for pre-implantation genetic screening. PGT-A is the newer nomenclature but both PGS and PGT-A are used interchangeably.
The doctor then explains the meaning of aneuploidy and euploidy. Aneuploidy refers to an incorrect number of chromosomes, namely if the embryo has an addition or a deletion of the whole chromosome or a part of the chromosome. If the embryo has euploidy, it means that there is the correct and complete number of chromosomes with no deletions or additions of the whole chromosome or a chromosome part.
Chromosomes are tiny packages of DNA. We have a total of 23 chromosomes from our father, 23 chromosomes from our mother – 46 chromosomes in total. We can map the chromosomes to check if we have a normal or abnormal complement of chromosomes. In order for us to understand the importance of the normal number of chromosomes, Dr Abramov describes the best-known aberrations in the number of chromosomes:
- trisomy 21 (Down syndrome),
- trisomy 18 (Edwards syndrome),
- trisomy 13 (Patau syndrome)
- and Turner syndrome (an example of chromosome deletion and a female condition).
Apart from the fact that all of these syndromes result in serious diseases, physical characteristics and malformations, they also be a cause of miscarriages. They are also often associated with advanced maternal age.
What are the reasons to perform the PGS
At this point the doctor considers why we should perhaps think about performing PGS. In fact, PGS is performed not so much to avoid Edwards, Down or Turner syndrome. It is mostly done to improve the chances that the pregnancy will be successful. According to the doctor, there’s also another advantage that PGS may have. A common thought is that if you transfer two or three embryos (that look good but did not undergo preimplantation genetic screening), you may increase the chances of at least one of them leading to a successful pregnancy. The problem with this approach is if the two embryos that are put back have a normal makeup of chromosomes. You then end up with twin pregnancies or even triplet pregnancies. These are pregnancies are high-risk pregnancies. So another advantage of PGS is making sure that the embryo you put back is a lot more likely to implant and you can put it back by itself without another sibling embryo and reduce the risk of multiple pregnancies.
What are the advantages of PGS?
As Dr Abramov summarises, there are a number of advantages of PGS. Firstly, you improve the pregnancy rate. Once you have an embryo with the normal makeup of chromosomes and you put it back, you can expect a pregnancy rate that is similar to that of a woman who is under the age of 35, regardless of her actual age. Secondly, you check whether the embryos have a normal complement of chromosomes in order to decrease the miscarriage rate or the multiple pregnancy race. In this way, you decrease the time to pregnancy, you shorten the fertility journey and you may also offer the patient a treatment plan which is more cost effective.
Dr Abramov also identifies the most ideal candidates for PGS IVF treatment. PGS is offered to women with advanced maternal age, who are more likely to have abnormal embryos. You could also use PGS in women who have multiple implantation failures or severe miscarriages history and to couples who have severe male factor infertility.
However, what is theoretically right very often does not stand the test of reality. Dr Abramov talks about some evidence and concerns that have been flagged up with the use of PGS. The British regulatory body HFEA has classified PGS as an ‘add-on’. The definition of an add-on is not necessarily the best term to be used: it is an emergent technique or technology that may have shown some promising results in initial studies or may have been around for a number of years, but has not necessarily been proven to improve pregnancy or birth rates.
Dr Abramov explains that we cannot say with 100% confidence that the application of PGS in IVF treatment is certain to be definitely advantageous. The HFEA uses a traffic light system to describe the strength of the evidence to support the use of add-ons. When it comes to PGS, its main disadvantage is that the procedure is in fact, a biopsy. The biopsy on day 3 has been given a red light which means that there is no evidence to say that this add-on is effective. Biopsy on day 5 has been given an amber sign, saying that there is a conflicting body of evidence for this add-on and further research is required.
Will PGS increase a patient’s overall chances?
The doctor highlights a very important argument: PGS will not increase a patient’s overall chances of having a baby. The question is how long will it get you toa point when you transfer this embryo. Without PGS the embryo with the normal number of chromosomes will be the last you transfer. In other words, PGS is essentially an embryo selection tool. However, the doctor admits that it is his practice to offer PGS to patients who have only one to two embryos not as an embryo selection tool but rather as a tool to reduce the impact of unsuccessful pregnancy on their emotional or psychological wellbeing. It will not guarantee a successful pregnancy but it will reduce the risk of ending up with another disheartening event: another miscarriage, another pre-term labour with another diagnosis of chromosomal abnormality.
What are the concerns with PGS?
There are two main concerns with PGS. There is a degree of risk that the biopsy as a procedure may cause damage to the embryos and therefore will reduce the overall chances of conception. You may end up hampering the chances of an embryo to implant although it has a normal complement of chromosomes. This happens because you removed a few cells from the layer of the cells that will become the placenta and the membranes. Another concern is that the cells sampled will not reflect the make-up of chromosomes of the entire embryos but rather represent a limited local area of abnormality. You may therefore end up discarding embryos which could have led to a successful pregnancy.
Another possibility you have to be ready for if you opt for PGS is that the result of the genetic tests might not conclusively identify the embryos as normal. The only thing you will know is that they are mosaic. It is therefore very difficult to ascertain whether you should transfer these embryos or you should refrain from transferring them. Under certain circumstances, when all the other embryos are abnormal and the only thing doctors have is a mosaic embryo, they do transfer such embryos. There are reports of normal pregnancies and babies that are delivered and they appear to be normal, too. Of course, the majority of such embryos will not implant or miscarry. But you cannot rule out a risk that such embryo would implant and end up with delivery of the baby who may be affected by a serious disability. This is another outcome of the PGS use which you should be aware of.